(2S,6S,11S)-6,11-Dimethyl-8-(1-phenyl-1H-tetrazol-5-yloxy)-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocine | 330198-33-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: (2S,6S,11S)-6,11-Dimethyl-8-(1-phenyl-1H-tetrazol-5-yloxy)-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocine
• CAS: 330198-33-9
• 化学式: C₂₁H₂₃N₅O
• 分子量: 361.447
• InChiKey: YSZPQNDEUSYMRA-RFVSGWPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.27
• 重原子数：
  27.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  64.86
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2S,6S,11S)-6,11-Dimethyl-8-(1-phenyl-1H-tetrazol-5-yloxy)-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocine 在 palladium on activated charcoal 作用下， 以 乙醇 、 环己烷 为溶剂， 反应 16.0h， 生成 (+)-5,9α-dimethyl-6,7-benzomorphan
  参考文献：
  名称：

  Synthesis and .sigma. Binding Properties of 2'-Substituted 5,9.alpha.-Dimethyl-6,7-benzomorphans

  摘要：

  The synthesis and sigma 1 and sigma 2 binding properties of several (+)- and (-)-2-benzyl- and 2-dimethylallyl-2'-substituted-5,9 alpha-dimethyl-6,7-benzomorphans (3 and 4) are presented. In agreement with previously reported binding data for 2-substituted 5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphans (N-substituted-N-normetazocine), all (1S,5S,SS)-(+)-isomers showed higher affinity for the sigma 1 site than the corresponding (1R,5R,9R)-(-)-isomers. Replacement of the 2'-hydroxy group of (+)-2-benzyl-5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphan [(+)-1f] with a 2'-NH2 and 2'-N(CH3)(2) [(+)-3b and (+)-3c, respectively] had only a small effect on the sigma 1 K-i values. Changing the 2'-hydroxy group of (+)-1f to an H, F, Cl, Br, I, NHAc, or NHSO2CH3 resulted in a 5-fold or greater loss in potency. In contrast, replacement of the 2'-hydroxy group of (+)-2-(dimethylallyl)-5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphan [(+)-1b, (+)-pentazocine] with a 2'-H or 2'-F group resulted in a 2-fold increase in potency. Conversion of (+)-1f to its 2'-desoxy analogue (+)-2d resulted in a 27.5-fold loss in affinity. This suggests that (+)-1f and other N-substituted benzomorphan analogues may be binding to single al receptors in a different way or to different sigma 1 receptors. (-)-Pentazocine [(-)-1b] and its 2'-fluoro analogue, (-)-2-(dimethylallyl)-5,9 alpha-dimethyl-2'-fluoro-6,7-benzomorphan [(-)-4a] showed the highest potency for the sigma 2 binding site.

  DOI：

  10.1021/jm00015a022
• 作为产物：
  描述：

  5-氯-1-苯基-1H-四唑 、 (2alpha,6alpha,11R*)-1,2,3,4,5,6-六氢-6,11-二甲基-2,6-甲桥-3-苯并氮杂环辛四烯-8-醇 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 25.0h， 以73%的产率得到(2S,6S,11S)-6,11-Dimethyl-8-(1-phenyl-1H-tetrazol-5-yloxy)-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocine
  参考文献：
  名称：

  合成和结合亲和力的顺式-（-）-和顺式-（+）-N-亚乙基氨基-N-去甲甲氧嘧啶类似物和顺式-（-）-N-甲甲氨酸类似物在σ1，σ2和κ阿片受体上的结合。

  摘要：

  描述了顺式（+）-和顺式-（-）-N-亚乙基氨基-N-去甲甲氧嘧啶类似物的合成，并评估了它们与sigma1，sigma2和κ阿片受体的亲和力。顺式（+）-脱氧化合物对sigma1受体的纳摩尔摩尔K（i）值显示出高的sigma / kappa选择性，而在顺式（-）-N-去甲甲唑嗪系列中发现化合物（-）-7b结合对Kappa阿片受体具有纳摩尔亲和力（K（i）= 21.5 nM）。与sigma1和sigma2位点以及mu和delta阿片受体相比，化合物（-）-7b对κ阿片受体表现出良好的选择性。

  DOI：

  10.1016/s0928-0987(00)00157-3